Pandemic preparedness improves national-level SARS-CoV-2 infection and mortality data completeness: a cross-country ecologic analysis.

BACKGROUND: Heterogeneity in national SARS-CoV-2 infection surveillance capabilities may compromise global enumeration and tracking of COVID-19 cases and deaths and bias analyses of the pandemic's tolls. Taking account of heterogeneity in data completeness may thus help clarify analyses of the relationship between COVID-19 outcomes and standard preparedness measures. METHODS: We examined country-level associations of pandemic preparedness capacities inventories, from the Global Health Security (GHS) Index and Joint External Evaluation (JEE), on SARS-CoV-2 infection and COVID-19 death data completion rates adjusted for income. Analyses were stratified by 100, 100-300, 300-500, and 500-700 days after the first reported case in each country. We subsequently reevaluated the relationship of pandemic preparedness on SARS-CoV-2 infection and age-standardized COVID-19 death rates adjusted for cross-country differentials in data completeness during the pre-vaccine era. RESULTS: Every 10% increase in the GHS Index was associated with a 14.9% (95% confidence interval 8.34-21.8%) increase in SARS-CoV-2 infection completion rate and a 10.6% (5.91-15.4%) increase in the death completion rate during the entire observation period. Disease prevention (infections: ß = 1.08 [1.05-1.10], deaths: ß = 1.05 [1.04-1.07]), detection (infections: ß = 1.04 [1.01-1.06], deaths: ß = 1.03 [1.01-1.05]), response (infections: ß = 1.06 [1.00-1.13], deaths: ß = 1.05 [1.00-1.10]), health system (infections: ß = 1.06 [1.03-1.10], deaths: ß = 1.05 [1.03-1.07]), and risk environment (infections: ß = 1.27 [1.15-1.41], deaths: ß = 1.15 [1.08-1.23]) were associated with both data completeness outcomes. Effect sizes of GHS Index on infection completion (Low income: ß = 1.18 [1.04-1.34], Lower Middle income: ß = 1.41 [1.16-1.71]) and death completion rates (Low income: ß = 1.19 [1.09-1.31], Lower Middle income: ß = 1.25 [1.10-1.43]) were largest in LMICs. After adjustment for cross-country differences in data completeness, each 10% increase in the GHS Index was associated with a 13.5% (4.80-21.4%) decrease in SARS-CoV-2 infection rate at 100 days and a 9.10 (1.07-16.5%) decrease at 300 days. For age-standardized COVID-19 death rates, each 10% increase in the GHS Index was with a 15.7% (5.19-25.0%) decrease at 100 days and a 10.3% (- 0.00-19.5%) decrease at 300 days. CONCLUSIONS: Results support the pre-pandemic hypothesis that countries with greater pandemic preparedness capacities have larger SARS-CoV-2 infection and mortality data completeness rates and lower COVID-19 disease burdens. More high-quality data of COVID-19 impact based on direct measurement are needed.

Establishing an incentive-based multistakeholder approach to dual-use DNA screening.

Fast, accessible, and high-quality deoxyribonucleic acid (DNA) is fundamental to advancement in the life sciences that will drive forward fields such as agriculture, energy, and medicine. Despite their importance in accelerating global progress, bioscience research and biotechnologies can also be misused, endangering humans, animals, and the environment. The ability to accidentally or deliberately endow or enhance the pathogenicity of biological systems is of particular concern. Access to DNA sequences with a clear potential for dual use should be limited to responsible and identifiable groups with legitimate uses. Yet, none of the 195 countries party to the International Health Regulations have national laws that mandate this type of screening. Many DNA providers voluntarily screen orders and absorb increased costs, but this practice is not universally adopted for a variety of reasons. This article explores the incentives and regulatory structures that can bring the screening coverage of DNA orders toward 100%, which may include expedited orders for approved customers, better tools and technology for more efficient screening, funding requirements that grantees use screened DNA, and early education in biosecurity aimed at researchers and students. Ultimately, an incentive-based multistakeholder approach to DNA screening can benefit researchers, industry, and global health security.

Evaluation of the Global Health Security Index as a predictor of COVID-19 excess mortality standardised for under-reporting and age structure.

BACKGROUND: Previous studies have observed that countries with the strongest levels of pandemic preparedness capacities experience the greatest levels of COVID-19 burden. However, these analyses have been limited by cross-country differentials in surveillance system quality and demographics. Here, we address limitations of previous comparisons by exploring country-level relationships between pandemic preparedness measures and comparative mortality ratios (CMRs), a form of indirect age standardisation, of excess COVID-19 mortality. METHODS: We indirectly age standardised excess COVID-19 mortality, from the Institute for Health Metrics and Evaluation modelling database, by comparing observed total excess mortality to an expected age-specific COVID-19 mortality rate from a reference country to derive CMRs. We then linked CMRs with data on country-level measures of pandemic preparedness from the Global Health Security (GHS) Index. These data were used as input into multivariable linear regression analyses that included income as a covariate and adjusted for multiple comparisons. We conducted a sensitivity analysis using excess mortality estimates from WHO and The Economist. RESULTS: The GHS Index was negatively associated with excess COVID-19 CMRs (table 2; ß= -0.21, 95% CI= -0.35 to -0.08). Greater capacities related to prevention (ß= -0.11, 95% CI= -0.22 to -0.00), detection (ß= -0.09, 95% CI= -0.19 to -0.00), response (ß = -0.19, 95% CI= -0.36 to -0.01), international commitments (ß= -0.17, 95% CI= -0.33 to -0.01) and risk environments (ß= -0.30, 95% CI= -0.46 to -0.15) were each associated with lower CMRs. Results were not replicated using excess mortality models that rely more heavily on reported COVID-19 deaths (eg, WHO and The Economist). CONCLUSION: The first direct comparison of COVID-19 excess mortality rates across countries accounting for under-reporting and age structure confirms that greater levels of preparedness were associated with lower excess COVID-19 mortality. Additional research is needed to confirm these relationships as more robust national-level data on COVID-19 impact become available.

Effect of COVID-19 on Household Food Insecurity and Poverty: Evidence from Ghana.

Following the outbreak of COVID-19 and its heavy toll on the global community and humanity, a fierce debate on the pandemic and Sustainable Development Goals (SDGs) performance nexus has emerged. While the literature on this subject remains highly contested, evidence within the Ghanaian contest is sparse. Thus, we present micro-level evidence on how COVID-19 poses a threat to hunger and poverty as SDGs in Ghana. Precisely, we examined the effect of COVID-19 on households' food insecurity and poverty and further analysed gender and locational sub-samples for differential effects. Data on 3905 households were obtained via concurrent online survey and telephone interviews. The results indicate that, on several occasions, a significant number of the sampled households (57.76%) did not get enough food to eat due to the pandemic. The proportion of households that went on several times without clean water for home use and access medicines/medical treatments were 50.52% and 52.22%, respectively. About 60.72% of the sampled households affirmed that, on several times, they did not have enough income due to the pandemic. At the same time, the share of households that suffered food insecurity due to the pandemic was 69.04%. Instrumenting for COVID-19 using distance to the affected communities, we find that a standard deviation increase in COVID-19 is associated with a rise of 0.232 and 0.289 standard deviations in poverty and food insecurity, respectively. Our results are robust to alternative estimation approaches to addressing the endogeneity of COVID-19 and other sensitivity checks. We conclude that Ghana would need to develop a new spectrum of gender- and location-sensitive policies that engender social inclusion as a conduit to expediate the attainment of zero poverty and hunger. Supplementary Information: The online version contains supplementary material available at 10.1007/s11205-021-02766-9.

Analysing COVID-19 outcomes in the context of the 2019 Global Health Security (GHS) Index.

INTRODUCTION: The Global Health Security Index benchmarks countries' capacities to carry out the functions necessary to prevent, detect and respond to biological threats. The COVID-19 pandemic served as an opportunity to evaluate whether the Index contained the correct array of variables that influence countries' abilities to respond to these threats; assess additional variables that may influence preparedness; and examine how the impact of preparedness components change during public health crises. METHODS: Linear regression models were examined to determine the relationship between excess mortality per capita for the first 500 days of countries' COVID-19 pandemic and internal Index variables, as well as external variables including social cohesion; island status; perceived corruption; elderly population size; previous epidemic experience; stringency of non-pharmaceutical interventions; and social and political polarisation. RESULTS: COVID-19 outcomes were significantly associated with sociodemographic, political and governance variables external to the 2019 Index: social cohesion, reduction in social polarisation and reduced perceptions of corruption were consistently correlated with reduced excess mortality throughout the pandemic. The association of other variables assessed by the Index, like epidemiological workforce robustness, changed over time. Fixed country features, including geographic connectedness, larger elderly population and lack of prior coronavirus outbreak experience were detrimental to COVID-19 outcomes. Finally, there was evidence that countries that lacked certain capacities were able to develop these over the course of the pandemic. CONCLUSIONS: Additional sociodemographic, political and governance variables should be included in future indices to improve their ability to characterise preparedness. Fixed characteristics, while not directly addressable, are useful for establishing countries' inherent risk profile and can motivate those at greater risk to invest in preparedness. Particular components of preparedness vary in their impact on outcomes over the course of the pandemic, which may inform resource direction during ongoing crises. Future research should seek to further characterise time-dependent impacts as additional COVID-19 outcome data become available.

Increased processing of SINE B2 ncRNAs unveils a novel type of transcriptome deregulation in amyloid beta neuropathology.

The functional importance of many non-coding RNAs (ncRNAs) generated by repetitive elements and their connection with pathologic processes remains elusive. B2 RNAs, a class of ncRNAs of the B2 family of SINE repeats, mediate through their processing the transcriptional activation of various genes in response to stress. Here, we show that this response is dysfunctional during amyloid beta toxicity and pathology in the mouse hippocampus due to increased levels of B2 RNA processing, leading to constitutively elevated B2 RNA target gene expression and high Trp53 levels. Evidence indicates that Hsf1, a master regulator of stress response, mediates B2 RNA processing in hippocampal cells and is activated during amyloid toxicity, accelerating the processing of SINE RNAs and gene hyper-activation. Our study reveals that in mouse, SINE RNAs constitute a novel pathway deregulated in amyloid beta pathology, with potential implications for similar cases in the human brain, such as Alzheimer's disease (AD).

Non-coding RNAs in virology: an RNA genomics approach.

Advances in sequencing technologies and bioinformatic analysis techniques have greatly improved our understanding of various classes of RNAs and their functions. Despite not coding for proteins, non-coding RNAs (ncRNAs) are emerging as essential biomolecules fundamental for cellular functions and cell survival. Interestingly, ncRNAs produced by viruses not only control the expression of viral genes, but also influence host cell regulation and circumvent host innate immune response. Correspondingly, ncRNAs produced by the host genome can play a key role in host-virus interactions. In this article, we will first discuss a number of types of viral and mammalian ncRNAs associated with viral infections. Subsequently, we also describe the new possibilities and opportunities that RNA genomics and next-generation sequencing technologies provide for studying ncRNAs in virology.

Ex-vivo iTreg differentiation revisited: Convenient alternatives to existing strategies.

Ex-vivo differentiation of regulatory T cells (Tregs) from naïve CD4+ T-cells has been widely used in immunological research. Isolation of a highly pure naïve T cell population is the key factor that determines the efficiency of subsequent Treg differentiation. Currently, this step relies mostly on FACS sorting, which is often costly, time consuming, and inconvenient. Alternatively, magnetic separation of T-cells can be performed; yet, available protocols fail to reach sort level purity and consequently result in low Treg differentiation efficiency. Here, we present the results of a comprehensive side-by-side comparison of various magnetic separation strategies and FACS sorting in multiple levels. Additionally, we propose a novel optimized custom made magnetic separation protocol, which not only yields sort level purity and Treg differentiation but also lowers the reagent costs up to 75% compared to the commercially available purification kits. The highly pure naïve CD4+ T-cell population obtained by this versatile method can also be used for differentiation of other T-cell subsets; therefore this protocol may have broad applications in T-cell research.